1. Field of the Invention
The present invention relates to a composition for the selective elimination of autoreactive B-cells comprising at least one (poly)peptide construct consisting of at least two domains wherein one of said domains comprises an autoreactive antigen or (a) fragment(s) thereof specifically recognized by the Ig receptors of said autoreactive B-cells and wherein one of said domains comprises an effector molecule capable of interacting with and/or of activating NK-cells, T-cells, macrophages, monocytes and/or granulocytes. Preferably, said composition comprises at least one (poly)peptide construct consisting of at least two domains, wherein said domain comprising an autoreactive antigen or (a) fragment thereof is MOG or (a) fragment(s) thereof and wherein said domain comprising an effector molecule is an anti-CD3 receptor or an Fc-part of an immunoglobulin. Described is also the use of the afore-mentioned (poly)peptide construct for the preparation of a pharmaceutical composition for the treatment and/or prevention of an autoimmune disease. In addition, the present invention relates to method for treating, ameliorating and/or preventing of an autoimmune disease.
2. Description of the Related Art
Several documents are cited throughout text of this specification. Each of the documents cited herein (including any manufacturer's specifications, instructions, etc.) are hereby incorporated by reference.
Autoimmunity results from the failure of the immune system in tolerating self-reactive lymphocytes, resulting in an adaptive immune response against self antigens. When such immune responses are sustained, they cause lasting tissue damage and are classified as autoimmune diseases.
Autoimmune diseases are generally divided into three types: B-cell dominant, T-cell dominant or combinational types. Pathogenic phenotypes of B-cell dominant autoimmune diseases are caused by circulating autoantibodies produced by autoreactive B-cells, while those of the T-cell dominant type are caused by direct tissue damage of activated T-cells against cells presenting autoreactive peptide-MHC complexes on their surface. Yet, these distinctions are not perspicuous, since B-cells and T-cells cooperate with and depend on each other in each type of autoimmune disease. Autoimmune diseases are classified as combinatorial when both autoreactive B- and T-cells contribute directly to the pathogenesis observed (“Immunobiology”, 4th edt. (1999), Chapter 13 pp 489-536, Janeway, C. A., Travers, P., Walport, M., Capra, J. D. eds and “Harrison's Principles in Internal Medicine”, 14th edt, Fauci, Braunwald, Isselbacher, Wilson, Martin, Kasper, Hauser, Longo, eds).